CHARACTERIZATION OF A CORONAVIRUS FROM RABBITS

本项目的目的是研究兔的发病机制

The objective of this project is to study the pathogenesis of rabbit coronavirus (RbCV), the rabbit's physiologic response to this virus, and the relatedness of RbCV to other members of the Coronaviridae. Serum neutralization studies against RbCV were extended using antiserum to human coronavirus (229-E). Two of 3 rabbits given RbCV treated with 229-E antiserum survived. All 3 exhibited clinical signs of disease but the 2 surviving rabbits had an accelerated recovery based on diminished eyes lesions and the body temperature returning to normal on post inoculation day 5 or 6. RbCV was purified on a sucrose density gradient and the bouyant density determined to be between 1.195 and 1.210. The bouyant density of 229-E determined at the same time was between 1.195 and 1.200. The RbCV recovered from the density gradient was infectious for rabbits and coronavirus like particles were seen by electron microscopy. Homology of RbCV and 229-E to transmissible gastroenteritis virus (TGEV) nucleic acid was demonstrated. This new data provides further proof for RbCV being a coronavirus of Group II related to 229-E. Purified RbCV is being used to make antibody in guinea pigs and rats for further studies of tissue tropisms. Assessment of myocardial damage by measurement of creatine kinase isozymes will be done. Attempts to adapt RbCV to tissue culture continue. Production of monoclonal antibodies and cloning of the RbCV genome are planned. The significance of this work lies in the ability to study a viral disease with a cardiotropism in an animal of sufficient but manageable size to allow sequential clinical and physiological observations. The damage to the rabbit heart by RbCV has a corollary in the human heart with the Coxsackie viruses. Mycoplasma pneumoniae, influenza virus, Herpes zoster, and possibly other infectious agents. Further, it has been estimated that approximately 10-30% of human "colds" are caused by coronaviruses.